DESCRIPTION (Investigator's Abstract): Magnetic fields will be used to confine the radial trajectories of electrospray ions and dramatically increase ion currents delivered to the mass analyzer. Sensitivity increases will be 100-fold for external source Fourier transform ion cyclotron resonance (FTICR) and greater than ten-fold for quadruple mass analyzers. The fundamental behavior of highly charged ions in combined magnetic and electric fields will be evaluated for the purposes of optimizing mass spectrometry performance. A high performance ESI/FTICR will be constructed in which the electroscopy is formed adjacent to the trapped ion cell and delivers nanoamp current into the cell. Careful control of ion kinetic energies will allow ions to accumulate in the cell to the space charge limit within a few hundred milliseconds. The investigators already demonstrated ESI/FTICR protein molecular weight range in excess of 100,000 Da will be extended beyond 500,000 Da. A differentially pumped concentric vacuum tube network will facilitate a pressure drop drom atm to 10-9 torr within a 25 cm region of the magnet bore. Consequently, FTICR high resolution capabilities will easily allow to charge state resolution for these ions and potentially isotope resolution for proteins up to the 250 kDa range.Unsurpassed FTICR mass accuracy in the m/z 1000 to 2000 range is simplified by availability of well characterized external calibrants and will permit accurate mass assignments to the low part-per-million level even for compounds beyond 100 kDa. The ability to control mass dependent ion kinetic energies out of source will be exploited in a tandem electric field/FTICR experiment to perform mixture analysis and thereby simplify the characterization of complex samples. The ability to trap ions will allow a variety of dissociation and reaction methodologies to be evaluated for the purpose of generating structural information. Collaborative arrangements with faculty performing biorelevant research will provide a radiology of challenging samples with which to carry out the electrospray experiments.